Characterization of insulin signaling in rat retina in vivo and ex vivo

Chad E.N. Reiter, Lakshman Sandirasegarane, Ellen B. Wolpert, Marianne Klinger, Ian Simpson, Alistair Barber, David A. Antonetti, Mark Kester, Thomas W. Gardner

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Insulin receptor (IR) signaling cascades have been studied in many tissues, but retinal insulin action has received little attention. Retinal IR signaling and activity were investigated in vivo in rats that were freely fed, fasted, or injected with insulin by phosphotyrosine immunoblotting and by measuring kinase activity. A retina explant system was utilized to investigate the IR signaling cascade, and immunohistochemistry was used to determine which retinal cell layers respond to insulin. Basal IR activity in the retina was equivalent to that in brain and significantly greater than that of liver, and it remained constant between freely fed and fasted rats. Furthermore, IR signaling increased in the retina after portal vein administration of supraphysiological doses of insulin. Ex vivo retinas responded to 10 nM insulin with IR β-subunit (IRβ) and IR substrate-2 (IRS-2) tyrosine phosphorylation and AktSer473 phosphorylation. The retina expresses mRNA for all three Akt isoforms as determined by in situ hybridization, and insulin specifically increases Akt-1 kinase activity. Phospho-AktSer473 immunoreactivity increases in retinal nuclear cell layers with insulin treatment. These results demonstrate that the retinal IR signaling cascade to Akt-1 possesses constitutive activity, and that exogenous insulin further stimulates this prosurvival pathway. These findings may have implications in understanding normal and dysfunctional retinal physiology.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number4 48-4
StatePublished - Oct 1 2003

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Insulin Receptor
Retina
Insulin
Phosphotransferases
Phosphorylation
Insulin Receptor Substrate Proteins
Phosphotyrosine
Portal Vein
Immunoblotting
In Situ Hybridization
Protein Isoforms
Immunohistochemistry
Messenger RNA
Liver
Brain

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Reiter, C. E. N., Sandirasegarane, L., Wolpert, E. B., Klinger, M., Simpson, I., Barber, A., ... Gardner, T. W. (2003). Characterization of insulin signaling in rat retina in vivo and ex vivo. American Journal of Physiology - Endocrinology and Metabolism, 285(4 48-4).
Reiter, Chad E.N. ; Sandirasegarane, Lakshman ; Wolpert, Ellen B. ; Klinger, Marianne ; Simpson, Ian ; Barber, Alistair ; Antonetti, David A. ; Kester, Mark ; Gardner, Thomas W. / Characterization of insulin signaling in rat retina in vivo and ex vivo. In: American Journal of Physiology - Endocrinology and Metabolism. 2003 ; Vol. 285, No. 4 48-4.
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Reiter, CEN, Sandirasegarane, L, Wolpert, EB, Klinger, M, Simpson, I, Barber, A, Antonetti, DA, Kester, M & Gardner, TW 2003, 'Characterization of insulin signaling in rat retina in vivo and ex vivo', American Journal of Physiology - Endocrinology and Metabolism, vol. 285, no. 4 48-4.

Characterization of insulin signaling in rat retina in vivo and ex vivo. / Reiter, Chad E.N.; Sandirasegarane, Lakshman; Wolpert, Ellen B.; Klinger, Marianne; Simpson, Ian; Barber, Alistair; Antonetti, David A.; Kester, Mark; Gardner, Thomas W.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 4 48-4, 01.10.2003.

Research output: Contribution to journalArticle

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